Implants are being employed in a wide variety of forms in modern medical technology. They are used, for example, to support vessels, hollow organs and vein systems (endovascular implants, such as stents), to fasten and temporarily fix tissue implants and tissue transplantations, but also for orthopedic purposes, such as nails, plates or screws.
The implantation of stents has become established as one of the most effective therapeutic measures for the treatment of vascular diseases. Stents have the purpose of performing a stabilizing function in hollow organs of a patient. To this end, stents of conventional build have a filigree support structure made of metal struts, which is initially present in compressed form for introduction into the body and is expanded at the site of the application. One of the main application areas of such stents is to permanently or temporarily dilate and hold open vascular constrictions, particularly constrictions (stenoses) of the coronary blood vessels. In addition, aneurysm stents are also known, which are used primarily to seal the aneurysm. The support function is additionally provided.
Stents include a peripheral wall with sufficient load-bearing capacity to hold the constricted vessel open to the desired extent and a tubular base body through which the blood continues to flow without impairment. The peripheral wall is generally formed by a lattice-like supporting structure, which allows the stent to be introduced in a compressed state, in which it has a small outside diameter, all the way to the stenosis of the particular vessel to be treated and to be expanded there, for example by way of a balloon catheter, so that the vessel has the desired, enlarged inside diameter. As an alternative, shape memory materials such as nitinol have the ability to self-expand when a restoring force is eliminated that keeps the implant at a small diameter. The restoring force is generally applied to the material by a protective tube until the implant is released.
The implant, notably the stent, has a base body made of an implant material. An implant material is a non-living material, which is used for applications in medicine and interacts with biological systems. A basic prerequisite for the use of a material as implant material, which is in contact with the body environment when used as intended, is the body friendliness thereof (biocompatibility). Biocompatibility shall be understood to mean the ability of a material to evoke an appropriate tissue response in a specific application. This includes an adaptation of the chemical, physical, biological, and morphological surface properties of an implant to the recipient's tissue with the aim of a clinically desirable interaction. The biocompatibility of the implant material is also dependent on the temporal course of the response of the biosystem in which it is implanted. For example, irritations and inflammations occur in a relatively short time, which can lead to tissue changes. Depending on the properties of the implant material, biological systems thus react in different ways. According to the reaction of the biosystem, the implant materials can be divided into bioactive, bioinert and degradable, for example resorbable, materials.
Implant materials include polymers, metallic materials, and ceramic materials (as coatings, for example). Biocompatible metals and metal alloys for permanent implants include, for example, stainless steels (such as 316L), cobalt-based alloys (such as CoCrMo cast alloys, CoCrMo forge alloys, CoCrWNi forge alloys and CoCrNiMo forge alloys), technical pure titanium and titanium alloys (such as cp titanium, TiAl6V4 or TiAl6Nb7) and gold alloys. In the field of biocorrodible stents, the use of magnesium or technical pure iron as well as biocorrodible base alloys of the elements magnesium, iron, zinc, molybdenum, and tungsten are proposed.
Stents comprising a coating for the local release of an active agent (referred to as local drug delivery (LDD) systems) have been known for quite some time and are widely used in practice. The drug is intended to prevent restenosis and, in some cases, additionally support the healing process. To this end, it is favorable to provide the antiproliferative active agent for preventing restenosis essentially only abluminally, because then it is primarily eluted into the vessel wall, where it is to take effect. The intent is to largely prevent a delay of the healing process on the luminal side of the stent by the antiproliferative active agent. The healing process can additionally be promoted by an appropriate second active agent that is luminally coated. The combination of a luminal with an abluminal coating further has the advantage that a form-fitting coating can be achieved, which considerably increases the mechanical stability of the coating.
Local differentiation of the active agent release is done in part with the aid of active agent reservoirs that are arranged on the surface of the stent. In addition, stent variants are known in which only a purely abluminal coating made of polymer and the active agent is applied. Moreover, systems in which differing active agents are released from polymer coatings abluminally and luminally have been described. WO 2010/120552 A1 describes stents that have a coating thickness that differs luminally from that which is present abluminally. Stents are also coated for other reasons, for example so as to influence the corrosion behavior of biocorrodible implant materials.
A number of methods have become established in industry for coating stents with active agents and other materials, such as polymers serving as the carrier matrix or corrosion protection purposes. These include spray-coating based on carrier gases, ultrasonic spraying, rotary spraying and rolling, as well as methods based on ink jet printing.
US 2008/0226812 A1 describes a coating apparatus which is able to coat both the luminal (inside of the stent) and abluminal (outside of the stent) surfaces. This is done with the aid of an ink jet printer, wherein the stent is rotated during coating. The method can also be employed to applying coatings including several layers.
US 2007/0288088 A1 describes the coating of a stent by way of spray-coating, in which the stent is rotated and the nozzle is located at a distance of 6.5 mm from the stent.
US 2011/0073036 A1 describes a device for coating the luminal surface of a stent. The device includes a sleeve that accommodates the stent during the coating process, wherein the stent is seated flush against the inside of the sleeve. Spray-coating on the luminal side of the stent is carried out by way of a movably mounted spray mandrel, which is inserted into the sleeve provided with the stent.
The coating methods and apparatuses of the prior art have the disadvantage that the differentiated application of the coatings to the luminal and abluminal sides of the stent is not possible or difficult. In addition, separately applied luminal or abluminal coatings frequently have lower stability, so that they can become detached from the implant in an uncontrolled manner.